Persistent hyperexcitability of the cell body (soma) of a primary sensory neuron may contribute to chronic pain, hyperalgesia and allodynia after a peripheral nerve injury. We will study the ionic mechanisms contributing to somal hyperexcitability, characterized, for example, by spontaneous activity and/or lowered thresholds and increased firing of action potentials resulting from a chronic compression of the dorsal root ganglion (DRG) (CCD). CCD, produced in the rat by the implantation of a rod into the intervertebral foramen, is a model of radicular pain in humans produced for example by a laterally herniated disk, stenosis or other degenerative or traumatic injuries of the spine. Extracellular and patch-clamp electrophysiological recordings will be used to compare responses to graded stimulation of the neuron's receptive field with the excitability of the soma followed by voltage-clamp recordings to identify characteristics of isolated voltage-gated sodium or potassium currents in the same cell that may contribute to somal hyperexcitability after CCD. We will test the hypothesis that CCD induced somal hyperexcitability is accompanied by alterations in the magnitude and kinetics of tetrodotoxin-sensitive (TTX-S) (fast transient and persistent) and TTX-resistant (TTX-R) voltage- gated sodium currents or, alternatively or in addition, to changes in the magnitude and kinetics of transient- inactivating or sustained-non-inactivating potassium currents. Our proposed studies will be able, for the first time, to link the voltage-gated currents of the soma with the response properties of its peripheral sensory terminals in different types of nociceptive and non-nociceptive sensory neurons. This approach will ultimately lead to the development of sensory specific anesthetics and analgesics that act selectively to block the pathological responses of specific kinds of primary sensory neurons.